Alpha-fetoprotein (AFP), a normal component of fetal and newborn sera, has been shown in the murine system to exert major differential effects, ranging from strong suppression to occasional enhancement, on both the recognitive and effector phases of the T cell-mediated cytotoxic reaction as measured in vitro in mixed leukocyte culture (MCL) and cell-mediated lympholysis (CML). AFP-induced suppressor/growth-promotor activity does not appear to follow the major T cell subclasses presently defined by Ly antigen phenotypes. Instead, the effect exerted by AFP is dependent on parameters controlled by the genetic relationship between responding and stimulating strains. This differential activity exerted by AFP on T cells provides the basis to utilize AFP as a selective reagent in the isolation of functional T cell subclasses. Suppressor activity of AFP selects against specific, although undefined, T cell subclasses, thereby permitting clonal expansion of AFP-refractive subclasses within the antigen-activated population, and at the same time, facilitating their isolation. Two AFP-refractive subclasses of T cells for which this technique selects are the "poised-cytoxic Ty lymphocyte" and a "suppressor T cell" capable of suppressing alloreactivity. Thus, major objectives of this resarch are (1) to determine which functional T cell subsets are susceptible and resistant to AFP-induced suppression, (b) to determine how these functional T cell subsets interact to create and regulate T cell-mediated cytotoxic reactions, (c) to investigate which cell-cell interactions are positively and negatively affected by AFP, and (d) to initiate studies to determine if results of these in vitro investigations have an in vivo relevance by utilizing the newborn mouse system. The newborn mouse has been chosen as an in vivo test system because of the high levels of circulating AFP presence during the first week post-partum. These studies should provide an insite into the mechanism of action of AFP as well as permit a new approach in dissection of the T cell-mediated cytotoxic reaction.